The morphology and function of the renal tubules have changed during the phylogenetic history of the vertebrates in order to adapt to their changing environment. We intend to define the physiological evolution of the renal tubule, which initially emerged as a primitive excretory device and culminated in the highly specialized mammalian kidney. During the current support period, we have determined renal function and renal responses to various natriuretic agents and transport inhibitors in intact teleost fishes and in vitro perfused fish renal tubules. We shall continue to study in vivo: 1) effect of diuretic drugs and vasoactive hormones in the aglomerular toadfish, Opsanus tau, to see whether the absence of glomerular circulation and the distal tubule influences renal responses; and 2) relationship between vasopressor and diuretic actions of neurohypophysial hormones in normally hydrated eels, Anguilla rostrata, and in eels with expanded extracellular fluid volume. Euryhaline teleosts can maintain their internal osmolality relatively constant regardless of the salinity of the environment, presumably by changing tubular permeability to water and maybe to electrolytes. However, there is no direct evidence to prove such an assumption except for some work on isolated urinary bladders. Using the established method of isolated perfused tubules from toadfish adapted to hypo- and hyperosmotic media and from freshwater catfish, we intend to define: 1) the mechanisms by which transtubular potential difference is generated; 2) the tubular permeability to water; 3) transport properties of sodium and relation of Na transport to water transport; and 4) effect of transport inhibitors, natriuretic drugs, and hormones on these parameters. Properties of hormone receptors may change when the fish are exposed to differing external environments. Comparative studies as proposed should provide better understanding of mammalian renal physiology.